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NanoBioSensors: From
Electrochemical Sensors
Improvement to Theranostic
Applications
Anielle C.A. Silva, Eliete A. Alvin, Lais S. de Jesus,
Caio C.L. de França, Marílya P.G. da Silva, Samaysa L. Lins,
Diógenes Meneses, Marcela R. Lemes, Rhanoica O. Guerra,
Marcos V. da Silva, Carlo J.F. de Oliveira,
Virmondes Rodrigues Junior, Renata M. Etchebehere,
Fabiane C. de Abreu, Bruno G. Lucca, Sanívia A.L. Pereira,
Rodrigo C. Rosa and Noelio O. Dantas
Abstract
1. Introduction
1
Biosensors - New Insights
Therefore, this chapter shows the innovative results obtained by the group of
carbon-based, semiconductor, and magnetic nanocrystals that can be used in biosen-
sors and biomedical applications, further strengthening the development of new
tools.
Figure 1.
Representation of the modification of the GCRE with RGO-CuNP, coupling of the modified sensor to the paper-
based electrochemical platform such as used in work, and voltammetric responses of unmodified and modified
electrodes in the simultaneous electroanalysis of paracetamol and caffeine.
applications. Another exciting feature of QDs is that properties such as size, shape,
composition, and structure can be controlled and tuned. It allows obtaining QDs with
unique properties according to the desired application [34, 35].
Although, promising, conventional QDs have some drawbacks that include
moderate stability, limited luminescence spectra, and large size to some applications.
At this point, the magic-sized quantum dots (MSQDs) are a class of nanocrystals that
show smaller particle sizes, broader spectra, and more excellent stability than conven-
tional QDs [36]. Among other applications, the MSQDs are a promising nanomaterial
for electrochemical sensing use. The small size (in nanometric scale) and the electri-
cal properties of these nanocrystals can significantly increase the surface area and the
conductivity of the sensors.
Our research group recently explored, for the first time, the application of MSQDs
for the modification of electrochemical sensors [37]. This pioneering work proposed
a simple and inexpensive paper electrochemical device (PED) whose carbon-based
working electrode was modified with CdSe/CdS MSQDs. The three-electrode setup
(working, counter, and pseudo-reference) was fabricated on the paper substrate by a
simple pencil-drawing method. At the same time, the CdSe/CdS MSQDs were synthe-
sized according to the method described by Silva et al. [36, 38, 39]. This PED was modi-
fied with CdSe/CdS MSQDs to demonstrate the analytical feasibility and applied for
clinical quantification of dopamine in biological samples, as represented in Figure 2.
Electrochemical and morphological techniques investigated the miniaturized
CdSe/CdS MSQDs-based PED. This modified PED presented improved analytical
signal (ca. 46% higher), lower charge transfer resistance (32 vs. 169 Ω), and larger
superficial area (0.28 vs. 0.14 cm2) in comparison with the unmodified PED. It can
be attributed to CdSe/CdS nanocrystals in the sensor, which was also confirmed by
microscopy analysis. The electroanalysis of dopamine in real human blood serum
samples was successfully carried out, and the limit of detection obtained was lower
than other recent reports that utilize more complex electrochemical platforms for
detecting the same analyte. In this way, MSQDs have been shown as a promising
nanomaterial to be explored in electrochemical sensing.
4
NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications
DOI: http://dx.doi.org/10.5772/intechopen.102552
Figure 2.
Picture of the paper electrochemical device containing the pencil-drawn carbon electrodes used in work,
representing a modification of the working electrode with CdSe/CdS MSQDs, and the voltammetric dopamine
response regarding the unmodified and modified electrodes.
In the last decade, several nanostructured systems for the delivery of chemothera-
peutic agents have been developed to eliminate tumor cells. However, most of these
systems cannot reach specific tumor cells without adequate control of these drug
release processes, resulting in serious side effects [40, 41]. It is necessary to direct
efforts to improve ideal drug distribution systems to release stimuli and selectively
target cancer cells. Thus, quantum dots, liposomes, magnetic nanoparticles, and TiO2
nanocrystals have enormous potential.
Quantum dots have been the subject of extensive investigations in different sci-
ence and technology areas in the past years [42, 43]. There are few studies of MSQDs,
even though they exhibit features such as tiny size, higher fluorescence quantum
efficiency, molar absorptivity greater than traditional QDs, and highly stable lumi-
nescence in theranostic, which refers to the simultaneous integration of diagnosis and
therapy [36, 39, 44, 45].
Our group investigated the first study about the core-shell MSQDs by analyzing
the electrochemical behavior of CdSe/CdS MSQDs immobilized on a gold electrode
modified with a self-assembled cyclodextrin monolayer using cyclic voltammetry
and electrochemical impedance spectroscopy techniques [46]. The work showed
a good interaction between the thiol group from thiolated cyclodextrin and CdSe/
CdS MSQDs (Figure 3a). The proposed method was successfully applied to encap-
sulation studies of Mangiferin, a natural antioxidant compound, and cyclodextrin
associated with the CdSe/CdS MSQDs, and the response was compared with that of
the modified electrode without MSQDs. The fluorescence study revealed that CdSe/
CdS MSQDs emit blue light when excited by an optical source of the wavelength
of 350 nm, and a significant increase in fluorescence and absorbance intensity is
observed from the core-shell CdSe/CdS MSQDs when quantities of Mangiferin
are added to the solution containing thiolated cyclodextrin. CdSe/CdS MSQDs are
optically and electrochemically sensitive and can be used to detect and interact with
compounds encapsulated in cyclodextrin and can be applied in theranostic.
Because of their reduced size, lipophilic nanoparticles of less than 100 nm can
cross the brain-blood barrier by diffusion, allowing the drug delivery directly to
the Central Nervous System (CNS) [47]. Neurodegenerative diseases (ND) such as
Alzheimer’s, Parkinson’s, strokes, glioblastoma, Huntington’s, amyotrophic lateral
5
Biosensors - New Insights
Figure 3.
(a) CdSe/CdS MSQDs immobilized on a gold electrode modified with a self-assembled cyclodextrin to
encapsulation studies of Mangiferin, and (b) illustration of liposome with MSQDs (top panel) when MSQDs are
(i) inside or (ii) outside and optical image the scale bar is 1 mm (bottom panel).
sclerosis may be treated differently with this approach [19]. Just like liposomes,
polymeric nanoparticles may be environmentally sensitive to drug release, such as
temperature change, pH change, among others. These systems may be combined
therapy, delivering two or more drugs, allowing different therapy combinations.
The group has also been developing liposomes containing CdSe/CdS MSQDs
aiming at a new luminescent tool for drug delivery. Figure 3b shows the illustration
of liposomes with MSQDs (top panel); when MSQDs are (i) inside or (ii) outside
and optical image, the scale bar is 1 mm (bottom panel). Therefore, we demonstrate
that CdSe/CdS MSQDs can be used in drug delivery systems, which serve as photo-
stable fluorescent reporters. A combination of MSQDs with liposomes is a powerful
6
NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications
DOI: http://dx.doi.org/10.5772/intechopen.102552
Figure 4.
Illustrative scheme of the nanocarrier composed by the PAMAN molecule, the black spheres represent the CoFe2O4
NCs and the LQM10 molecule.
7
Biosensors - New Insights
The porous structure of TiO2 nanotubes increases bone regeneration and repair,
presenting good osteointegration, being used as a graft and biological fixation ele-
ment for implants [57, 65–70]. In an experimental study carried out by our research
group using TiO2 NCs, adequate osteointegration in bone failure in the calvary of rats
was evidenced, with the presence of a large amount of newly formed tissue, suggest-
ing effective osteoinductive action, as can be seen in Figure 5.
Despite the promising findings with TiO2 NCs, it is essential to report that there
may be a high contamination rate and post-surgical infection since, currently, the
spread of antibiotic-resistant bacteria is a worrying threat to human health.
In this context, it is essential to establish new antimicrobial strategies, in which
the idea of coating device surfaces with active antimicrobial metals is considered one
of the essential strategies. Therefore, bimetallic corrosion is inevitable, in which TiO2
photocatalytic nanomaterials, in the anatase form, offer more significant advantages
for antimicrobial purposes [71]. Still, the photocatalytic activity of TiO2 under
exposure to ultraviolet radiation results in disinfectant properties, mainly related to
the generation of reactive oxygen species [72].
In this perspective, the sensitive and accurate detection of biological analytes in
low concentrations is another application of TiO2 nanostructures that is beneficial
for biomedical research and clinical diagnosis. There has been significant interest
in applying TiO2 detection in biosensors [57, 67]. Therefore, those reported in the
literature point out that TiO2 nanocrystals are inert and safe structures when exposed
to the human organism, thus contributing to new promising nanotechnologies with
the biomedical application.
Luminescence is related to some materials’ ability to light emissions. This excita-
tion energy (absorbed energy) can be obtained from different sources: photons
usually in the ultraviolet region of the electromagnetic spectrum (emission called
photoluminescence), electrical energy (electroluminescence), electron beam (cath-
odoluminescence), physical impact (gives rise to triboluminescence) and heating the
luminophore (results in thermoluminescence) [73, 74]. Photoluminescent materials
are often called phosphors or luminophores [73]. Efficient luminophore requirements
are efficient absorption of light in a suitable spectral region; chemical stability of the
excited electronic state populated after light absorption; high conversion efficiency
to the excited luminescent state; a long lifetime of excited state luminescence; high
luminescent efficiency [75].
Photoluminescent materials require a host crystalline matrix, such as TiO2, as
well as an activating ion, such as lanthanides. Lanthanide ions are known to have
Figure 5.
Histological section of rats’ calvaria: (a) fibrous connective tissue (asterisk); bone tissue (arrow); and (b) TiO2
NCs (arrows), bone tissue (arrow), and neoformed fibrous connective tissue (asterisk) (hematoxylin and eosin
staining, 400×).
9
Biosensors - New Insights
Figure 6.
Fluorescence microscopy of mesenchymal stem cells treated with europium doped TiO2 NCs: (a) culture medium
with 50 μg of mesenchymal stem cells; and (b) culture medium with 100 μg of mesenchymal stem cells.
3. Conclusion
Therefore, this chapter showed nanocrystals inserted in biosensors and their use
in drug delivery tools or biomaterials. Graphene and magic-sized quantum dots into
biosensors enable an increase in sensitivity and specificity, making the development
of nanotechnological platforms in biological diagnosis possible. In theranostic applica-
tions, magic-sized quantum dots, magnetic nanoparticles, and TiO2 nanocrystals can be
innovative drug delivery tools and dental and orthopedic applications. Thus, the fabri-
cation of nanomaterials with interesting properties makes it possible to generate several
potential tools to improve electrochemical sensors and in theranostic applications.
Acknowledgements
Conflict of interest
Author details
Anielle C.A. Silva1,2*, Eliete A. Alvin1,2, Lais S. de Jesus1, Caio C.L. de França3,
Marílya P.G. da Silva3, Samaysa L. Lins3, Diógenes Meneses3, Marcela R. Lemes4,
Rhanoica O. Guerra4, Marcos V. da Silva4, Carlo J.F. de Oliveira4,
Virmondes Rodrigues Junior4, Renata M. Etchebehere5, Fabiane C. de Abreu3,
Bruno G. Lucca6, Sanívia A.L. Pereira7,8, Rodrigo C. Rosa9 and Noelio O. Dantas1
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of
the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
11
Biosensors - New Insights
References
ACS Nano. 2014:8, 1913-1922. cancer. In: Recent Studies & Advances in
DOI: 10.1021/nn406478f Breast Cancer. Wilmington: Open Access
eBooks; 2017. pp. 1-10
[39] Almeida Silva A, Silva MJ, da Luz FA,
Silva D, de Deus S, Dantas N. Controlling [46] de Lima França CC, da Silva
the cytotoxicity of CdSe magic-sized Terto EG, Dias-Vermelho MV, Silva ACA,
quantum dots as a function of surface Dantas NO, de Abreu FC. The
defect density. Nano Letters;14:5452-5457. electrochemical behavior of core-shell
DOI: 10.1021/nl5028028 CdSe/CdS magic-sized quantum dots
linked to cyclodextrin for studies of the
[40] Lammers T, Subr V, Ulbrich K, encapsulation of bioactive compounds.
Hennink WE, Storm G, Kiessling F. Journal of Solid State Electrochemistry.
Polymeric nanomedicines for image- 2016;20:2533-2540. DOI: 10.1007/
guided drug delivery and tumor- s10008-016-3221-8
targeted combination therapy. Nano
Today. 2010;5:197-212. DOI: 10.1016/j. [47] Mansoor KR, Sima KR, Soheila KR.
nantod.2010.05.001 Advancement of polymer–based
nanoparticles as smart drug delivery
[41] Zahednezhad F, Zakeri-Milani P, systems in neurodegenerative medicine.
Shahbazi Mojarrad J, Valizadeh H. The Journal of Nanomedicine Reseasrch.
latest advances of cisplatin liposomal 2019;8:277-280. DOI: 10.15406/
formulations: Essentials for preparation jnmr.2019.08.00198
and analysis. Expert Opinion on
Drug Delivery. 2020;17:523-541. [48] Alving CR, Steck EA, Chapman WL,
DOI: 10.1080/17425247.2020.1737672 Waits VB, Hendricks LD, Swartz GM,
et al. Therapy of leishmaniasis: Superior
[42] Kargozar S, Hoseini SJ, Milan PB, efficacies of liposome encapsulated
Hooshmand S, Kim HW, Mozafari M. drugs. Proceedings of the National
Quantum dots: A review from concept Academy of Sciences of the United
to clinic. Biotechnology Journal. States of America. 1978;75:2959-2963.
2020;15:e2000117. DOI: 10.1002/ DOI: 10.1073/pnas.75.6.2959
biot.202000117
[49] Cheng R, Liu L, Xiang Y, Lu Y,
[43] Wagner AM, Knipe JM, Orive G, Deng L, Zhang H, et al. Advanced
Peppas NA. Quantum dots in biomedical liposome-loaded scaffolds for therapeutic
applications. Acta Biomaterialia. and tissue engineering applications.
2019;94:44-63. DOI: 10.1016/j. Biomaterials. 2020;232:119706.
actbio.2019.05.022 DOI: 10.1016/j.biomaterials.2019.119706
16
NanoBioSensors: From Electrochemical Sensors Improvement to Theranostic Applications
DOI: http://dx.doi.org/10.5772/intechopen.102552
17
Biosensors - New Insights
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